Thymopentine treatment improves clinical and immunological functions in aged subjects with chronic bronchitis.

The effect of in vivo thymopentine treatment (50 mg/subcutaneously every other day for six weeks) on clinical features and in vitro immunological parameters was evaluated in ten aged patients with chronic bronchitis. In vitro immunological studies were performed before and after treatment both on phenotypic (OK monoclonal defined lymphocyte subpopulations) and functional parameters (blastogenic responses to polyclonal mitogens Concanavalin-A and Phytoemagglutinine). Thymopentine did not significantly affect lymphocyte subpopulations, which were reduced before pharmacological treatment, when compared to those of young healthy controls. Peripheral blood lymphocytes blastogenic response to polyclonal mitogens was restored, even though proliferation did not reach the values of young healthy subjects. Thymopentine treatment significantly improved lymphocyte functions, without being able, however, to overcome completely the age-dependent loss of blastogenic responses. Nevertheless the favourable evolution of clinical symptoms we observed in our study may be, at least in part, related to the improvement in vivo of those immunological functions that we studied in vitro. Eight out of ten patients showed an evident improvement of symptoms and signs of chronic bronchitis after thymopentine treatment and four of them arrived to a complete remission from infectious episodes. No side effects were noted. Although still preliminary, these results seem to be encouraging as thymopentine could be used with success as an immunomodulating agent in aged people.

Evidence for adenosine adenosinedeaminase lymphocyte system impairment in ageing.

Age related immune disfunctions are the result of humoral and cellular changes of the immune system and reflect major alterations of T cell subpopulations which concern cyclic nucleotides and their precursors. There are now many reports showing that adenosine can affect some phenotypic and functional lymphocyte characteristics. We have found that a short preincubation (30') with adenosine can inhibit proliferative responses of peripheral blood lymphocytes to polyclonal mitogen Concanavalin A in young healthy controls (p less than 0.05) but not in aged healthy subjects. These data led us to the hypothesis that an impairment of the adenosine-adenosinedeaminase system could play an important role in the age-associated decline of immune responses. Our results show a highly significant reduction (16.45 +/- 3.56 vs 24.42 +/- 9.5 p less than 0.001) of adenosinedeaminase activity in peripheral lymphocytes of aged humans (mean age 75.5 +/- 6.7 range 23-30). Preliminary studies suggest that this alteration could be responsible to some extent, for the decreased mitogenic response of lymphocytes reported in ageing.

Impairment of lymphocyte-suppressive system in recent-onset insulin-dependent diabetes mellitus. Correlation with metabolic control.

Impairment of suppressor-cell activity may be important in the pathogenesis and maintenance of insulin-dependent diabetes mellitus (IDDM). In 23 recent-onset IDDM patients, lymphocyte sensitivity in vitro to theophylline was tested both in basal conditions and after improvement of metabolic control. This pharmacologic agent is mainly effective on a lymphocytic subpopulation with phenotypic and functional suppressive features. Peripheral blood lymphocytes from IDDM patients showed a loss of theophylline sensitivity, identified as inhibition of both E-rosette formation and blastogenic response to polyclonal mitogens concanavalin A (ConA) and phytohemagglutinin (PHA). An inverse relationship was demonstrated between the theophylline-induced suppression of ConA blastogenic response and blood glucose and glycosylated hemoglobin levels (P less than .01). Metabolic control seemed to be important even in relation to lymphocyte subpopulation distribution. In IDDM patients we found a significant (P less than .05) reduction of OKT4+ lymphocytes that is correlated with blood glucose and glycosylated hemoglobin levels (P less than .01). The improvement of metabolic control led to recovery of theophylline sensitivity. We suggest a deficiency in a suppressive system that could be involved in IDDM onset and the possible role of metabolic control in the impairment of some immunologic functions reported with this pathologic condition.

[Cutaneous reactions to ubiquitous antigens in a young population hospitalized for minor pathologies]. / Reattività cutanea ad antigeni ubiquitari in una popolazione giovane ospedalizzata per patologie minori.

Delayed hypersensitivity was evaluated by means of skin testing with ubiquitous antigens (Candidin, Tricophytin, Varidase and PPD) in a population of 233 young subjects (mean age 21 years, range 19-24) referred to the Army Hospital of Milan for minor pathologies. The results show a high incidence of anergies (20.1%) and hypoergies (50.9%) in the sample studied and low percentages of positive responses to Candidin (12.45%), Tricophytin (3%) and PPD (15.9%). A significant enhancement of the percentages of anergic subjects has also been observed in two subgroups selected on the basis of blood lymphocyte count (less than 1250 cells/mm2) (p less than 0.01) and on gamma-globulin levels (greater than 1.5 g/100 ml) (p less than 0.05). The observed findings are discussed.

In vivo effects of a single infusion of theophylline on human peripheral blood lymphocytes.

It has recently been proposed that theophylline activates T suppressor systems in vivo and this evidence is further supported by the ability of the drug to attenuate the allograft rejection in humans and in experimental animals. In this study the acute effects of aminophylline on human peripheral blood lymphocyte (PBL) mitogenic responses have been investigated. PBL from healthy young volunteers who received intravenous aminophylline (5 mg/kg i.v. over 20 min) showed an increased proliferative response to phytohaemagglutinin. This was correlated with an augmented OKT4/OKT8 ratio, due to an absolute increase in the OKT4+ subset as well as a decrease in OKT8+ cells. Furthermore, following in vivo aminophylline we observed a significant rise in lymphocyte cAMP levels. These data, together with studies from other laboratories, suggest that the dosages and duration of treatment may influence greatly the theophylline-induced modulation of immune functions.

Spontaneous "in vitro" variations of theophylline sensitivity in human peripheral blood lymphocytes.

Theophylline reversibly inhibits E rosette formation by a portion of human circulating T lymphocytes. We investigated the effect of theophylline on E rosette formation and intracellular content of cyclic nucleotides (cAMP, cGMP). When the amine is added to 15 human healthy donors' lymphocytes either before or after 24 hours of culture at 37 degrees C, in absence of mitogens, a portion of theophylline-sensitive T cells spontaneously becomes theophylline-resistant after 24 hours of culture. While the intracellular content of cAMP does not significantly vary, the ability of theophylline to induce an increase of cAMP appears to be impaired after 24 hours of culture. The possible correlation between theophylline resistance and impaired turnover of cAMP in the cultured lymphocytes is discussed.

Increase of T.G lymphocytes in human one-way mixed lymphocyte culture.

Human one-way mixed lymphocyte culture induces a significant increase of EA(7S) rosette-forming cells. Using fractionation procedures, an increased number of Fc receptor-bearing cells in the T high-enriched populations was found from alloactivated lymphocytes compared with similar fractions obtained after autologous control cultures. Additional experiments showed a parallel increase of E-rosette-forming cells in the Fc receptor-enriched alloactivated fractions. The results indicate that an increase of T.G lymphocytes occurs during in vitro alloactivation in man.

Human lymphocyte surface markers after allogeneic activation: increase of Fc receptors-bearing cells.

The behaviour of human lymphocyte surface markers was investigated after in vitro alloactivation. Evidence was obtained that the expression of surface receptors is modified during mixed lymphocyte culture. In vitro allogeneic stimuli are able to induce a very significant increase of Fc receptors bearing cells: the biological significance of these data is discussed.

T cell defect in essential mixed cryoglobulinaemia.

Peripheral blood lymphocytes from untreated patients with essential cryoglobulinaemia were studied for their surface markers and for their in vitro mitogenic reactivity. No differences in lymphocyte subpopulations were observed between cryoglobulinaemic patients and normal controls. Cultures of separated lymphocytes were stimulated with different concentrations of phytohaemagglutinin, Con-A and pokeweed mitogen. Incorporation of [3H]-thymidine in patients' cultures was compared with that of normal controls. Significantly decreased reactivity to phytohaemagglutinin and Con-A, but not to pokeweed mitogen, was found in all patients studied. The depressed mitogenic reactivity to phytohaemagglutinin and Con-A might be referred to a qualitative T cell defect.